• Newest desig­na­tion for JNJ-4528 is sup­ported by Phase 1b/2 CARTITUDE-1 study in adults with re­lapsed or re­frac­tory mul­ti­ple myeloma
• Initial re­­sults from CARTITUDE-1 study to premiere at the American Society of He­ma­tol­ogy Annual Meeting

{{image}}Raritan, NJ (Press Release) – The Janssen Pharma­ceu­tical Com­panies of John­son & John­son an­nounced to­day that the U.S. Food and Drug Admin­istra­tion (FDA) has granted Break­­through Therapy Desig­na­tion for JNJ-68284528 (JNJ-4528), an inves­ti­ga­tional B cell maturation an­ti­gen (BCMA)-directed chi­meric an­ti­gen re­cep­tor T cell (CAR-T) ther­apy in pre­vi­ously treated patients with mul­ti­ple myeloma. Break­­through Therapy Desig­na­tion is granted to expedite the devel­op­ment and regu­la­tory re­view of an inves­ti­ga­tional med­i­cine that is in­tended to treat a serious or life-threatening con­di­tion. The criteria for Break­­through Therapy Desig­na­tion re­quire pre­lim­i­nary clin­i­cal evi­dence that dem­onstrates the drug may have sub­stan­tial im­prove­ment on at least one clin­i­cally sig­nif­i­cant end­point over avail­able ther­apy.

"The granting of Break­­through Therapy Desig­na­tion for JNJ-4528 is a sig­nif­i­cant mile­stone as we con­tinue to ac­cel­er­ate the global devel­op­ment of this inno­va­tive CAR-T ther­apy in col­lab­o­ration with Legend Biotech," said Sen Zhuang, M.D., Ph.D., Vice Pres­i­dent, Oncology Clinical De­vel­op­ment, Janssen Re­search & De­vel­op­ment, LLC. "We look for­ward to continuing to work closely with the U.S. Food and Drug Admin­istra­tion to ad­vance the clin­i­cal devel­op­ment pro­gram for JNJ-4528 and ultimately bring this BCMA-targeted immuno­therapy to patients living with mul­ti­ple myeloma who are in need of a new thera­peutic op­tion."

The Break­­through Therapy Desig­na­tion is sup­ported by data from the Phase 1b/2 CARTITUDE-1 study (NCT03548207), an open-label, multi­center clin­i­cal trial eval­u­ating the safety and ef­fi­cacy of JNJ-4528 in adults with re­lapsed or re­frac­tory mul­ti­ple myeloma who have re­ceived at least three prior lines of ther­apy or are double re­frac­tory to a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory drug (IMiD); have re­ceived a PI, IMiD and an anti-CD38 anti­body; and who progressed on or within 12 months of their last line of ther­apy.¹ Currently active in the U.S., the pri­mary objective of the Phase 1b portion of the study is to char­ac­ter­ize the safety of JNJ-4528 and con­firm the dose for future clin­i­cal trials. Phase 2 is eval­u­ating ef­fi­cacy with a pri­mary end­point of over­all re­sponse­ rate, as defined by the Inter­na­tional Myeloma Work­ing Group re­sponse­ criteria, as well as duration of re­sponse­ and over­all tol­er­a­bil­ity. Initial data from the CARTITUDE-1 study will be pre­sented for the first time at the American Society of He­ma­tol­ogy Annual Meeting (Abstract #577).

The CARTITUDE-1 study design was in­formed by the Phase 1 LEGEND-2 study (NCT03090659), the first-in-human study with LCAR-B38M CAR-T cells.² In Feb­ru­ary 2019, the FDA granted Janssen an Orphan Drug Desig­na­tion for JNJ-4528. On April 3, 2019, Janssen an­nounced the Euro­pean Medicines Agency granted a PRIME (PRIority MEdicines) desig­na­tion for JNJ-4528 based on the CARTITUDE-1 and LEGEND-2 stud­ies.

JNJ-4528, a structurally dif­fer­en­ti­ated CAR-T with two BCMA-targeting single domain anti­bodies, identifies the inves­ti­ga­tional prod­uct being studied in the U.S. and Europe.³ LCAR-B38M, which has the same CAR con­struct, identifies the inves­ti­ga­tional prod­uct in China. In De­cem­ber 2017, Janssen entered into a world­wide col­lab­o­ration and license agree­ment with Legend Biotech to jointly de­vel­op and com­mer­cial­ize LCAR-B38M in mul­ti­ple myeloma. In China, the Phase 2 CARTIFAN-1 con­firmatory trial (NCT03758417), sponsored by Nanjing Legend Biotech Co. Ltd. in col­lab­o­ration with Janssen, is actively recruiting to fur­ther eval­u­ate LCAR-B38M in patients with ad­vanced re­lapsed or re­frac­tory mul­ti­ple myeloma.⁴

About CAR-T and BCMA

CAR-T cells are an inno­va­tive ap­proach to eradicating can­cer cells by har­nessing the power of a patient's own im­mune sys­tem. BCMA is a pro­tein that is highly ex­pressed on myeloma cells.

About CARTITUDE-1

CARTITUDE-1 (NCT03548207) is an on­go­ing Phase 1b/2, open-label, multi­center study eval­u­ating the safety and ef­fi­cacy of JNJ-68284528 in adults with re­lapsed or re­frac­tory mul­ti­ple myeloma who have re­ceived at least three prior lines of ther­apy or are double re­frac­tory to a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory drug (IMiD); have re­ceived a PI, IMiD and an anti-CD38 anti­body; and who progressed on or within 12 months of their last line of ther­apy.1 The pri­mary objective of the Phase 1b portion of the study is to char­ac­ter­ize the safety and con­firm the dose of JNJ-68284528, which was in­formed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The pri­mary objective for the Phase 2 portion of the study is to eval­u­ate the ef­fi­cacy of JNJ-68284528 (primary end­point: over­all re­sponse­ rate as defined by the Inter­na­tional Myeloma Work­ing Group re­sponse­ criteria).

About Multiple Myeloma

Multiple myeloma is an incurable blood can­cer that affects a type of white blood cell called plasma cells, which are found in the bone mar­row.^5,6 When damaged, these plasma cells rapidly spread and re­place nor­mal cells with tumors in the bone mar­row.^5,6 In 2019, it is esti­mated that more than 32,000 people will be diag­nosed, and nearly 13,000 will die from the dis­ease in the United States.⁷ While some patients with mul­ti­ple myeloma have no symp­toms, most patients are diag­nosed due to symp­toms, which can in­clude bone fracture or pain, low red blood cell counts, tiredness, high cal­cium levels, kidney prob­lems or in­fec­tions.⁸

About the Janssen Pharma­ceu­tical Com­panies of John­son & John­son

At Janssen, we're creating a future where dis­ease is a thing of the past. We're the Pharma­ceu­tical Com­panies of John­son & John­son, work­ing tirelessly to make that future a reality for patients every­where by fighting sickness with science, im­prov­ing access with ingenuity, and heal­ing hope­less­ness with heart. We focus on areas of med­i­cine where we can make the biggest dif­fer­ence: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal and www.twitter.com/JanssenUS. Janssen Re­search & De­vel­op­ment, LLC and Janssen Biotech, Inc. are members of the Janssen Pharma­ceu­tical Com­panies of John­son & John­son.

Cautions Concerning Forward-Looking State­ments

This press re­lease con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing prod­uct devel­op­ment and the poten­tial ben­e­fits and treat­ment im­pact of JNJ-4528. The reader is cautioned not to rely on these for­ward-looking state­ments. These state­ments are based on cur­rent ex­pec­ta­tions of future events. If under­lying assump­tions prove inaccurate or known or un­known risks or un­cer­tainties ma­teri­alize, actual re­­sults could vary ma­teri­ally from the ex­pec­ta­tions and pro­jec­tions of Janssen Re­search & De­vel­op­ment, LLC or any of the other Janssen Pharma­ceu­tical Com­panies and/or John­son & John­son. Risks and un­cer­tainties in­clude, but are not lim­ited to: chal­lenges and un­cer­tainties in­her­ent in prod­uct re­search and devel­op­ment, in­clud­ing the un­cer­tainty of clin­i­cal success and of obtaining regu­la­tory ap­prov­als; un­cer­tainty of com­mer­cial success; manu­fac­tur­ing dif­fi­culties and delays; com­pe­ti­tion, in­clud­ing tech­no­log­i­cal ad­vances, new prod­ucts and pat­ents attained by com­pet­i­tors; chal­lenges to pat­ents; prod­uct ef­fi­cacy or safety con­cerns re­sult­ing in prod­uct recalls or regu­la­tory action; changes in be­havior and spending pat­terns of pur­chasers of health care prod­ucts and services; changes to appli­cable laws and reg­u­la­tions, in­clud­ing global health care reforms; and trends to­ward health care cost con­tainment. A fur­ther list and descriptions of these risks, un­cer­tainties and other factors can be found in John­son & John­son's Annual Report on Form 10-K for the fiscal year ended De­cem­ber 30, 2018, in­clud­ing in the sections cap­tioned "Cautionary Note Regarding Forward-Looking State­ments" and "Item 1A. Risk Factors," and in the com­pany's most recently filed Quar­ter­ly Report on Form 10-Q, and the com­pany's sub­se­quent filings with the Se­cu­ri­ties and Ex­change Com­mis­sion. Copies of these filings are avail­able online at www.sec.gov, www.jnj.com or on re­quest from John­son & John­son. Neither the Janssen Pharma­ceu­tical Com­panies nor John­son & John­son under­takes to up­date any for­ward-looking state­ment as a re­­sult of new in­for­ma­tion or future events or devel­op­ments.

References

1. ClinicalTrials.gov. A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Par­tic­i­pants With Re­lapsed or Re­frac­tory Multiple Myeloma. NCT03548207. Available at: https://clinicaltrials.gov/ct2/show/NCT03548207. Accessed De­cem­ber 2019.
2. ClinicalTrials.gov. LCAR-B38M-02 cells in treating re­lapsed / re­frac­tory (R/R) multiple myeloma (LEGEND-2). NCT03090659. Available at: https://clinicaltrials.gov/ct2/show/NCT03090659. Accessed De­cem­ber 2019.
3. Fan F. Poster presented at the 17th Inter­na­tional Myeloma Workshop, Sep­tem­ber 12-15, 2019; Boston, MA. Abstract number FP-181, #413.
4. ClinicalTrials.gov. A Study of LCAR-B38M CAR-T Cells, a Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Chinese Par­tic­i­pants With Re­lapsed or Re­frac­tory Multiple Myeloma (CARTIFAN-1). NCT03758417. Available at: https://clinicaltrials.gov/ct2/show/NCT03758417. Accessed De­cem­ber 2019.
5. Kumar SK, et al. Leukemia. 2012 Jan; 26(1):149-57.
6. American Cancer Society. "What Is Multiple Myeloma?." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed De­cem­ber 2019.
7. American Cancer Society. "Key Statistics for Multiple Myeloma." Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed De­cem­ber 2019.
8. American Cancer Society. "Diagnosing Multiple Myeloma From Test Results." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed De­cem­ber 2019.

Source: Janssen.